Carlo Rostagno

Prognostic value of 6‐minute walk corridor test in patients with mild to moderate heart failure: comparison with other methods of functional evaluation

The study was designed to evaluate the prognostic value of the 6‐min walk test (6MWT) in patients with mild to moderate congestive heart failure (CHF).

Acute T-cell activation is detectable in unstable angina.

BACKGROUND Recent studies suggest a role for inflammation in the pathophysiology of unstable angina. This study was designed to investigate whether circulating lymphocytes are involved in the inflammatory reaction associated with the episodes of unstable angina. METHODS AND RESULTS Twenty-nine patients with proven unstable angina, 36 with stable angina, and 30 healthy subjects were studied. Both early and short-lived (interleukin-2 receptor [IL-2R], alpha-chain CD25, and transferrin receptor CD71) and late antigen (HLA-DR) expression were investigated by flow cytometric analysis. Soluble IL-2R (sIL-2R) was also measured in plasma by ELISA. Lymphocyte activation was studied at day 1 of hospital admission and after 7, 15, 30, 60, and 90 days. In patients with unstable angina, the number of HLA-DR+ CD3 lymphocytes and levels of sIL-2R were higher (P < .001) than in patients with stable angina and control subjects. Both CD4+ and CD8+ lymphocytes expressed HLA-DR antigens. No differences were found among the different groups of subjects in regard to the expression of CD25 and CD71. Lymphocyte activation was more marked in patients with urgent revascularization. No relationships were found between the number of HLA-DR+ lymphocytes and either the severity of coronary angiographic lesions or the number of ischemic episodes. Observations over time showed a gradual decrease in the number of HLA-DR+ lymphocytes and sIL-2R levels from weeks 3 through 8 to 12. CONCLUSIONS The present results indicate that (1) CD4+ and CD8+ circulating lymphocytes are activated in patients with unstable angina, and their activation state lasts 6 to 8 weeks; and (2) activation of lymphocytes is not a consequence of myocardial ischemia. These results support the immune system-mediated inflammatory nature of unstable angina.

Effect of heparin, aspirin, or alteplase in reduction of myocardial ischaemia in refractory unstable angina

399 out of 474 inpatients with unstable angina were monitored for 48 h and 97 of these were found to be refractory to conventional antianginal treatments and entered a randomised double-blind study. With the initial protocol heparin infusion or bolus were compared with aspirin; with a modified protocol, heparin infusion, the best of these three treatments, was compared with alteplase. Patients were monitored for 3 days after starting treatment and then observed clinically for 4 more days. On the first days of treatment heparin infusion significantly decreased the frequency of angina (by 84-94%), episodes of silent ischaemia (by 71-77%), and the overall duration of ischaemia (by 81-86%). Heparin bolus and aspirin were not effective. Alteplase caused small (non-significant) reductions on the first day only. Only minor bleeding complications occurred.

Small-dose recombinant activated factor VII (NovoSeven) in cardiac surgery.

Recombinant activated factor VII (rFVIIa) has been used at different doses in cardiac surgery patients. We tested the efficacy of small-dose rFVIIa in patients with intractable bleeding after cardiac surgery. The study group comprised 15 cardiac surgery patients with intractable bleeding treated with small-dose (1.2 mg) rFVIIa as a slow IV bolus at the end of complete step-by step transfusion protocol. Fifteen matched patients undergoing the same transfusion protocol in the pre-rFVIIa era represented the control group. Blood loss at the end of the transfusion protocol was a primary outcome. Median, 25th–75th 24-h blood loss percentiles were 1685 (1590–1770) mL versus 3170 (2700–3850) mL in study group and controls, respectively (P = 0.0004). Transfused red blood cells, fresh-frozen plasma, and platelets in the study group and controls were as follows: 7 (4–8) U versus 18 (12–21) U (P = 0.001); 7.5 (6–11) U versus 11 (9–15) U (P = 0.003); 0 (0–4) U versus 9 (6–13) U (P = 0.001). In addition, significant improvements of prothrombin time (P = 0.015), international normalized ratio (P = 0.006), activated partial prothrombin time (P = 0.01), and platelet count (P = 0.003) were detected in the study group versus controls. Finally, patients receiving rFVIIa showed a reduced intensive care unit length of stay (&khgr;2 = 15.9, P = 0.0001) and had infrequent surgical re-exploration (&khgr;2 = 16.2,P < 0.0001). Small-dose rFVIIa showed satisfactory results in cardiac patients with intractable bleeding. Further randomized studies are necessary to confirm our findings.

Age-related changes in the hemostatic system

SummaryThe increased incidence of arterial thromboembolism in the elderly has prompted investigation of age-related changes in the hemostatic system. Aging is associated with increased plasma levels of fibrinogen, factor VII and factor VIII, which have been shown to be risk factors for thrombotic disease in five large epidemiological studies. An increased responsiveness to different aggregating stimuli, elevated levels of β-thromboglobulin and an increased production of thromboxane A2 were reported in the platelets of the elderly. These alterations are associated with modifications of platelet membrane lipid composition (namely an increase in the cholesterol/phospholipid ratio and a decrease in linoleic acid) with possible related changes in membrane fluidity. Moreover, a decrease in the number of platelet prostacyclin and thromboxane A2 receptors was observed with aging. Fibrinolytic activity is impaired in the elderly, probably due to an increase in plasminogen activator inhibitor 1. Interestingly, hypercoagulability has been demonstrated by an increase in the activation markers of the coagulation cascade (mainly fibrinopeptide A and prothrombin activation fragment F 1+2). Finally, clinical and experimental evidence suggests that endothelium could play a central role in hemostatic alterations which determine a thrombophilic state in the elderly.

The onset of symptomatic atrial fibrillation and paroxysmal supraventricular tachycardia is characterized by different circadian rhythms

Abstract Circadian patterns have been demonstrated for several biologic phenomena including cardiovascular diseases such as acute myocardial infarction and sudden death.1 Diurnal distribution of paroxysmal supraventricular arrhythmias has been less extensively investigated,2,3 but only data on hospitalized patients are available. The aim of this study was to find if a diurnal distribution could be identified in the occurrence of the different types of symptomatic supraventricular arrhythmias in patients rescued at home by the Florence Mobile Coronary Care Unit.

Six minute walk test: a simple and useful test to evaluate functional capacity in patients with heart failure

In heart failure survival is closely related to functional capacity. Peak O2 consumption at cardiopulmonary exercise test (CPET) is considered the gold standard for the evaluation of exercise tolerance. Since >70% of patients with heart failure, usually elderly or with significant comorbidities, are referred to Departments of Internal Medicine where facilities for cardiopulmonary test are rarely available, CPET may be performed in <5% of the patients. Six-minute walk test (6MWT) has been proposed as a simple, inexpensive, reproducible alternative to CPET. The 6MWT reproduces the activity of daily life and this is particularly relevant in elderly patients who usually develop symptoms below their theoretical maximal exercise capacity. Despite some limits 6MWT is attractive for patients referred to Departments of Internal Medicine allowing an objective evaluation of exercise tolerance, a better prognostic evaluation and a guide to evaluate response to medical treatment.

Comparison of different methods of functional evaluation in patients with chronic heart failure

Stratification of the severity of heart failure has major prognostic and therapeutic implications.

Insights on left ventricular and valvular mechanisms of recurrent ischemic mitral regurgitation after restrictive annuloplasty and coronary artery bypass grafting

BACKGROUND We investigated leaflet and subvalvular configurations to identify mechanisms leading to recurrent mitral regurgitation after combined undersized mitral annuloplasty and coronary artery bypass and to preoperatively recognize patients who are unlikely to benefit from this approach. METHODS Among 261 subjects with chronic ischemic mitral regurgitation undergoing undersized annuloplasty and coronary bypass surgery at one institution between September 2001 and September 2007, 31 were excluded: 4 had intraoperative annuloplasty failure, 12 showed residual regurgitation, and 15 had incomplete echocardiograms available. The study population consisted of 230 patients who were divided into 2 groups: patients without (group 1, n = 176) or with (group 2, n = 54) late recurrent mitral regurgitation. Fifty healthy subjects were used as control subjects. Serial echocardiographic analysis was performed preoperatively, at discharge, and at follow-up appointments (early: median, 6 months [interquartile range, 5-6 months; late: median, 33 months [interquartile range, 17-51 months]). RESULTS Subjects with late regurgitation had preoperatively more symmetric tethering (P < .001), more accentuated anterior mitral leaflet tethering (P < .001), and more restricted anterior leaflet excursion (P = .003) than patients in group 1. Postoperatively, tethering of the posterior leaflet increased (P < .001) and was predominant in both groups, whereas tethering of the anterior leaflet was reduced at discharge (P = .01 and P = .03, respectively), remaining constant afterward. Multivariable analysis showed an anterior tethering angle of 39.5 degrees or greater (P < .001), an anterior/posterior tethering angle ratio of 0.76 or greater (P < .001), an anterior leaflet excursion angle of 35 degrees or less (P = .001), and a coaptation height of 11 mm or greater (P = .04) to be predictors of recurrent mitral regurgitation. CONCLUSIONS Preoperative symmetric tethering with anterior mitral leaflet predominance was strongly associated with recurrence of mitral regurgitation. Measures of leaflet tethering resulted in fundamental findings to identify ischemic patients who can really benefit from restrictive annuloplasty. Further larger studies are necessary to confirm our results.

Left Ventricular Reverse Remodeling After Undersized Mitral Ring Annuloplasty in Patients With Ischemic Regurgitation

BACKGROUND Long-term durability of combined coronary artery bypass grafting and of undersized mitral ring annuloplasty (UMRA) is uncertain. A considerable number of patients show recurrent regurgitation. This study examines the difference in the benefit of UMRA on clinical end points and recurrence of mitral regurgitation between responders and nonresponders of left ventricular reverse remodeling. METHODS Study eligibility criteria were fulfilled by 204 patients with chronic ischemic mitral regurgitation (CIMR) who survived combined coronary artery bypass grafting and reductive annuloplasty between September 2001 and September 2006. Patients underwent echocardiography preoperatively, at discharge, and at follow-up appointments (100% complete). Median early follow-up was 6 months (interquartile range [IRQ], 3 to 8 months; late follow-up, 35 months (IRQ, 21 to 50 months). Reverse remodeling was considered a reduction in left ventricular end systolic volume index exceeding 15%. RESULTS There were 84 responders (41.2%) of reverse remodeling (age, 68 +/- 7.4 years; 51 men) and 120 nonresponders (58.8%; age, 67 +/- 7.6 years; 78 men). Nonresponders had a higher recurrence of mitral regurgitation (p < 0.001), higher reoperation rate for failed repair (p < 0.001), and significantly larger left ventricular volumes and dimension at any study point (p < 0.001), with significant late increase of sphericity indexes exceeding preoperative values (p < 0.001). At multivariable analysis, a baseline myocardial performance index of less than 0.90 (p < 0.001), a systolic sphericity index of less than 0.72 (p < 0.001), and wall motion score index of less than 1.59 (p = 0.003) were independent predictors of reverse remodeling. CONCLUSIONS Our experience suggests that more information on possible echo predictors of an inadequate result may improve preoperative decision making of CIMR patients for UMRA.